Shape-Defined microPlates for the Sustained Intra-articular Release of Dexamethasone in the Management of Overload-Induced Osteoarthritis.
Shape-Defined microPlates for the Sustained Intra-articular Release of Dexamethasone in the Management of Overload-Induced Osteoarthritis.
复制标题
用于关节内持续释放地塞米松治疗超负荷引起的骨关节炎的形状限定微板。
DOI：
10.1021/acsami.1c02082
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发表时间：
2021-07-14
影响因子：
9.5
通讯作者：
Decuzzi P
中科院分区：
文献类型：
--
作者：
Di Francesco M;Bedingfield SK;Di Francesco V;Colazo JM;Yu F;Ceseracciu L;Bellotti E;Di Mascolo D;Ferreira M;Himmel LE;Duvall C;Decuzzi P
骨关节炎（OA）是通过关节内注射类固醇如地塞米松（DEX）来治疗的，以提供短期疼痛管理。然而，DEX治疗遭受快速关节清除。在这里，创建了20 × 10 μm形状确定的聚（d，l-丙交酯-共-乙交酯）酸微板（μ PL），并在关节内沉积，用于DEX的持续释放。在密闭条件下，预计DEX释放将持续数月，第一个月仅释放约20%。在高度严格的鼠膝关节过载损伤模型（创伤后骨关节炎）中，在软骨表面、髌下脂肪垫/滑膜、关节囊和后关节间隙中检测到Cy 5-μ PL的单次关节内注射长达30天。在治疗后4周，与游离DEX相比，一次关节内注射DEX-μPL（1 mg kg-1）使白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、IL-6和基质金属蛋白酶（MMP）-13的表达降低约一半。相对于生理盐水或游离DEX，DEX-μPL还减少了关节软骨和滑膜组织中负荷诱导的组织学变化。总之，μ PL提供持续的药物释放沿着精确控制颗粒几何形状和机械性质的能力，在过载诱导的OA中产生持久的益处。这项工作激发了进一步研究和开发提供组合药理学和机械益处的颗粒。
Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 μm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (μPLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only ∼20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-μPLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-μPL (1 mg kg–1) decreased the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-μPL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the μPLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.
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影响因子：
33.7
作者：
Bajpayee, Ambika G.;Grodzinsky, Alan J.
通讯作者：
Grodzinsky, Alan J.
DOI：
10.1016/j.nano.2015.01.011
发表时间：
2015-05-01
影响因子：
5.4
作者：
Cho, Hongsik;Pinkhassik, Eugene;Hasty, Karen A.
通讯作者：
Hasty, Karen A.
影响因子：
16.1
作者：
Gao W;Chen Y;Zhang Y;Zhang Q;Zhang L
通讯作者：
Zhang L
DOI：
10.1038/nrrheum.2015.158
发表时间：
2016-02
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Huang Z;Kraus VB
通讯作者：
Kraus VB
影响因子：
8.4
作者：
Chen, Shoubing;Wang, Qihua;Pei, Xianqiang
通讯作者：
Pei, Xianqiang